Dioxin-like Chemical Messenger Makes Brain Tumours More Aggressive

Using drugs to inhibit this metabolic pathway is a new approach in cancer treatment. Glioma is the most frequent and most malignant brain tumour in adults. In Germany, about 4,500 people are newly diagnosed with glioma every year. About 75 per cent of such tumours are considered particularly aggressive with an average life expectancy of eight months to two years. The standard treatment is surgery to remove the tumour as completely as possible, followed by radiotherapy, usually in combination with chemotherapy. However, results are unsatisfactory, because these tumours are very resilient and soon start growing back. Therefore, there is an urgent need for new treatment approaches.

The Helmholtz Junior Research Group “Experimental Neuroimmunology” led by Professor Michael Platten of DKFZ and the Department of Neurooncology of Heidelberg University Hospital and the National Centre for Tumour Diseases (NCT) headed by Professor Wolfgang Wick have come across the kynurenin molecule in their studies of human cancer cells and in the mouse model. Kynurenin is formed when the amino acid tryptophan – a protein component taken in with food – is broken down in the body. “We have been able to detect increased levels of kynurenin in cancer cells of glioma patients with particularly aggressive tumours,” Platten explained. The current research results from Heidelberg show that this link also appears to exist in other types of cancer such as cancers of the bladder, bowel or lungs.

It was even more astonishing for the investigators to find that kynurenin activates a protein known as dioxin receptor. This, in turn, triggers a cascade of chemical reactions which ultimately promote tumour growth and weaken the immune system. So far, it had only been known that the dioxin receptor, scientifically called aryl hydrocarbon receptor (AHR), is activated by environmental toxins. “Why this receptor is even present in body cells and which is its activation partner in the body, was yet unknown,” says Doctor Christiane Opitz. “Kynurenin seems to have very similar effects as dioxin, but it is formed by the body itself,” said Platten.

The newly discovered metabolic pathway is a potential target for cancer treatment. The intention is to inhibit tumour growth and strengthen the immune system. “We will start searching for substances that specifically inhibit this metabolic pathway and may be used as potential antitumor drugs,” said Wick envisioning the next steps ahead.